Transcript principles of management of stimulant misuse

PRINCIPLES OF
MANAGEMENT OF STIMULANT
MISUSE
DR ALISON BATTERSBY
Amphetamine
• Class of synthetic drugs similar effect to
adrenalin
• Act by releasing noradrenalin and
dopamine and inhibiting reuptake.
• D and L forms (D twice as powerful as a
central stimulant)
Group of compounds
• Amphetamine
• Methamphetamine
• Fenfluramine
• Bupropion
• Mephedrone
• Synthesised in Germany in 1887
• Nasal decongestants until 1930’s
• Medically tested on hospital workers in
30’s to create wellbeing and relieve fatigue
• WW11 to combat fatigue
• OTC in 50’s, POM in 60’s
• Second most commonly injected drug
Effects
• Elevated mood
• Feel more energetic, alert and self-
confident
• Improved task performance
• Decreased fatigue and hunger
• May be more talkative, restless or agitated
• Increased libido
• Increased heart rate, BP
• Palpitations
• Dilated pupils
• Dry mouth
• Sweating
• L-amphetamine greater cardiovascular
effects
Intoxication
• Dizziness
• Sweating
• Chest pain
• Palpitation
• Hypertension
• Cardiac arrhythmias
• May increase body temp/convulsions
Tolerance
• To some but not all aspects
• To gain euphoric effect may need to
escalate dose
• Cardiovascular effects
• Appetite suppression
• Used therapeutically for narcolepsy and
hyperkinetic disorders
Physical Dependence
• Disputed
• After a “run” abrupt withdrawal “the
crash”
• Fatigue, depression, hunger
• Irritability
• Anxiety/agitation
• ?normal reaction
Psychological dependence
• Definitely present
• Intense craving
• drug-seeking behaviour
• Powerful reinforcer in animal experiments
Adverse effects
• Psychotic illness
• Often persecutory in nature
• Automatic stereotyped behaviour
• Irritability
• Paranoia
• Aggression
Mode of Action Dopamine and
Serotonin
• Causes presynaptic dopamine vesicles to release
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dopamine into cytosol
Causes reversal of the DAT (dopamine active )
transporters so it transports Dopamine into the
cleft
Reversal of the SERT (serotonin) transporter
particularly in mesocorticolimbic pathways
increasing glutamatergic neurons
Physical Sequelae
• Cardiovascular, HT, Pulse, cardiomyopathy,
aortic dissction
• CNS ischaemic strokes, intracerebral
haemorrhages, seizure, abnormal
movements
• Ischaemic colitis
• Rhabdomyolysis
• hepatotoxicity
Methamphetamine
• Common nicknames, ice, crystal meth,
crank, glass, speed, shabu (philippines),
tik (south africa) and ya ba (thailand)
• Oral, snorting, smoking, injection
Pharmacology
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½ life 9-15 hrs excreted by kidney
Lipid soluble, fast entry to brain
Resistance to MAO degradation
Causes reversal of dopamine, NA uptake
enzymes
Tolerance occurs partially due to transmitter
depletion
Neurotoxic to dopamine and serotonin neurons
Effects
• Desired: euphoria, alertness,
concentration, self confidence, energy
• Unwanted: aggression, agitation,
irritability, paranoia, psychosis
• Physical: anorexia, tachycardia,
hypertension, constipation, palpitations,
stroke, MI, convulsions
Production
• Combination of red phosphorus,
pseudoephedrine and iodine
• Extremely dangerous
Long term effects
• Meth mouth, dry mouth, grinding teeth
• Injecting related problems
• Unsafe sex
• Withdrawal: excessive sleeping, increased
appetite and depression, often
accompanied by anxiety and drug craving
Amphetamine psychosis
• 309 regular amphetamine users
• 13% screened positive for psychosis
• 23% clinically significant symptoms of
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suspiciousness, unusual thought content or
hallucinations in the past year
Swift onset
Delusions and hallucinations may mimic bipolar
or schizophrenia
Abates within days with restoration of sleep and
cessation of amphetamines
Treatment of Amphetamine
Dependence
• Mainly semi-structured psychosocial
interventions
• Substitution therapies, evidence is
equivocal or poor quality
• Occasional use of modafinil, baclofen,
mirtazapine and naltrexone
• High dose venlafaxine/SSRI’s when use
stopped
Cocaine
• Alkaloid prepared from coca bush
• Erythroxylum coca
• Central and south america
• Leaves chewed alleviate fatigue, hunger
and cold
• Incas religious ceremonies, social and
medicinal
• First isolated 1880’s
• Oral consumption widespread
• Used in tonics
• Freud noted local anaesthetic and psychic
effects
• Recommended it for treatment opiate
addiction
Coca-cola (old-style)
Manufacture
• Illegal factories close to growth
• Cocaine hydrochloride obtained
• White powder
• Easy to transport
• Cut eg sugar, amphetamine, beta blockers
Route of administration
• Sniffing/snorting (line inhaled through
straw)
• Vasoconstriction of blood vessels
• No rush, 20-40minute effect
• Rhinitis/perforated nasal septum
• Iv
• Smoking
• Cocaine hydrochloride unsuitable for
smoking (decomposes high temps)
• Alkaloid can be freed from hydrochloride
by using ether, vaporises easily
Crack
• Cooking cocaine with baking powder and
water
• Baking powder precipitates impurities
• Pure crystalline cocaine
• Usually smoked in pipe or sprinkled on
cigarette
• Sudden intense high
• Reaches brain within seconds
• Euphoria abates quickly
• User feels restless and irritable
• Marked craving
• Use often escalates quickly to chase the
high
Effects
• CNS stimulant
• Increased energy, wakefulness, activity
and confidence
• Powerful euphoriant eg Brompton cocktail
• Raised pulse, blood pressure, temperature
• Dilated pupils
• Local vasoconstriction
Very high doses
• Hypertension
• Cardiac arrythmias
• Convulsions
• Death (cardiac/respiratory arrest)
Tolerance
• Some degree of tolerance with pure
cocaine freebase
• Ceiling tolerance level
• No tolerance to reinforcing effect
Physical dependence
• Withdrawal
• Crash thirty minutes after a binge
• Social withdrawal, depression, tremor,
muscle pain, disturbance of sleeping,
eating
• Dysphoria, intense craving
• Extinction phase 3-12 months
Psychological dependence
• Severe
• Animal model, powerful reinforcer
• Mechanism of action not fully understood
• Specific cocaine receptors
• Affects dopaminergic system, inhibit
dopamine reuptake
Long-term use
• Excessive dopamine metabolised
• Therefore reduced dopamine
concentration
• Then changes in post-synaptic receptors
(craving)
• Also acts on NA and 5HT systems
inhibiting reuptake
Cocaine toxicity/psychosis
• Anxiety, restlessness, apprehension,
suspiciousness, hypervigilence, paranoid
behaviour
• Muscle twitching, nausea, vomiting
• Increase pulse and blood pressure
• Irregular respiration
• convulsions
Severe toxicity
• Circulatory failure
• Respiratory failure
• Loss of reflexes
• Unconsciousness
• death
Cocaine psychosis
• Persecutory delusions
• Stereotyped behviour
• Auditory hallucinations
• Tactile hallucinations (cocaine bugs)
Treatment
• Not as well defined as for opiate addiction
• Psychosocial interventions using semistructured interviews
• Acupuncture
Ketamine
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Developed 1962 by Pfizer
Used as a general anaesthetic or in pain relief
NMDA (Glutamate) receptor antagonist
Action particularly in the prefrontal cortex and
hippocampus
At higher levels binds opioid receptors, partial
D2 agonist and inhibits dopamine reuptake
Illicit use
• Sold in powder or liquid
• Can be sniffed, injected or swallowed
• Significant first pass metabolism so larger
amounts needed if swallowed
• Class C drug
• Dependence rare, tolerance develops
reasonably quickly, no abstinence
syndrome?
Effects
• Dissociative amnesia k-hole
• Feelings of detachment from the world:
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depersonalisation/derealisation
Spiritual experiences
Feeling connected to others
Visual hallucinations, other perceptual
abnormalities
Changes in time
Lasts about 2 hours
Health consequences
• Bladder problems- BMJ 2008 case series of 9
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patients dose-related
Severe urinary frequency, urgency, macroscopic
haematuria, suprapubic pain
Changes in cognition, heavy users worse verbal
short-term memory and visual memory
Occasional users no different from controls
Overdose, commonly from iv use
Questions please
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